Treating COPD With Mucolytics

One of the key features of the chronic obstructive pulmonary disease (COPD) is the excessive production of mucus in the lungs. This overproduction, sometimes referred to as chronic mucus hypersecretion, is caused by long-term inflammation which increases both the number and size of so-called "goblet cells" that line the air passages.

While goblet cells normally secrete mucus as a form of protection, with COPD the excessive production can clog the passages, making it harder to breathe.

One way of clearing this buildup is with an oral or nebulized drug called a mucolytic. Mucolytics work by dissolving the chemical bonds within the secretions, breaking them so they can be more readily coughed up.

While mucolytics are not considered part of the current standard of care for COPD treatment, the 2017 guidelines issued by the Global Initiative for Obstructive Lung Disease (GOLD) suggest that they may be useful in persons not receiving inhaled corticosteroids.

Mucolytics can be taken orally in a tablet or syrup formulation or inhaled through a nebulizer. Some of the more common types of used in COPD include:

• Carbocysteine
• N-acetylcysteine
• Erdosteine
• Mecysteine
• Guaifenesin
• Bromhexine

The mechanism of action can vary by drug. Carbocysteine, for example, acts on the metabolism of the goblet cells and also offers antioxidant and anti-inflammatory benefits. N-acetylcysteine, by contrast, breaks up the bonds that hold the mucus together while altering the imbalance of oxidants and antioxidants.

The side effects can also vary both by drug type and formulation. Broadly speaking, nausea and diarrhea are the most common side effect associated with tablets, while liquid symptoms may also cause bronchial spasms and rashes. Nebulized formulations can similarly cause a sore throat, runny nose, and the formation of white patches in the mouth or lips.

By and large, mucolytics are considered safe and associated with a low risk of adverse events in people with COPD. With that being said, it's always important to speak with your doctor about any side effects, interactions, or contraindications associated with a mucolytic product, whether prescribed or purchased over the counter. 

Despite the widespread use of mucoactive drugs in COPD, the current evidence is not very supportive of their effectiveness.

A 2015 review of 34 trials did conclude that those who took mucolytics were less likely to experience COPD exacerbations. In analyzing the results, however, this translated to a relatively modest reduction of one exacerbation for every three years. Other studies have more or less drawn similar conclusions.

Yet, despite these shortcomings, some have argued that mucolytics have a place in COPD treatment. Given the concerns about the safety of long-term corticosteroid use, there have been suggestions that they may be appropriate in advanced COPD wherein the risk of exacerbation is high irrespective of steroid use. Mucolytics may, in these cases, help reduce the number of exacerbations and offer some improvement in the quality of life.

One substudy associated with the Bronchitis Randomized on NAC Cost-Utility Study (BRONCUS) further concluded that, when used with an inhaled corticosteroid, mucolytic drugs may reduce COPD exacerbations by as much as 21 percent. 

Mucolytics may also be helpful in persons who are intolerant of inhaled corticosteroids or have difficulty with handheld inhalers.